L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications in the agri-food ...sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel's salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against
,
,
, and
. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on
and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (
/
). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.
Organic pollutants (OPs) and heavy metals are environmental toxicants associated with great concerns. Decontamination processes are urgent for both, and the possibility to achieve their simultaneous ...removal from polluted waters is highly interesting. Additionally, in many cases, the effect of organic matter in the removal process is overlooked and must be considered. This work aimed to study the potential of alginate-based and polycaprolactone (PCL) materials to remove OPs and copper ions in the absence and presence of organic matter. The OPs investigated were the polycyclic aromatic hydrocarbons anthracene and benzoapyrene, and the pesticide chlorpyrifos, both hydrophobic compounds. Copper (II) ions were used as a model of heavy metals. Alginate-based spheres were prepared by gelation, and PCL microparticles were obtained by oil/water emulsion solvent evaporation. The materials with the highest efficiencies for OP removal from aqueous solutions were those with activated carbon and PCL. Furthermore, the spheres with activated carbon could remove anthracene and copper simultaneously, even in the presence of humic acid. This work points to activated carbon–alginate spheres as a multifunctional adsorbent able to remove different pollutants and to PCL for potential applications in OP decontamination processes.
Crithmum maritimum L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications ...in the agri-food sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel’s salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermis, Candida albicans, and Candida parapsilosis. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on Lactobacillus bulgaricus and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (w/v). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.
A presente investigação insere-se no âmbito do Projecto A Par em Portugal, inspirado pelo Peers Early Education Partnership de Inglaterra. Pretende analisar o desenvolvimento da função parental, de ...pais com crianças entre os três e os cinco anos, ao nível da Gratificação Parental, Actividades de Interacção Pais-Filhos e Apoio Social através de três instrumentos, em fase de adaptação. Nos estudos preliminares foram realizadas análises acerca da qualidade psicométrica de cada um dos instrumentos separadamente, com diferentes amostras de sujeitos, através dos quais encontrámos bons índices de precisão e validade. Os instrumentos revelaram-se como pluridimensionais. No estudo principal, que pretendia averiguar a relação entre as variáveis, analisámos as respostas de 68 pais (mães ou pais). As correlações permitiramnos verificar a existência de relações positivas entre todas as variáveis: um aumento da Gratificação Parental será acompanhado de mais Actividades de Interacção e maior percepção de Apoio Social por parte dos pais. Além disso, evidenciaram-se resultados significativos ao nível de algumas variáveis sócio-demográficas, como a idade da criança (com o Apoio Social e a Gratificação Parental), as habilitações académicas da mãe, a idade da mãe, a idade do pai (com o Apoio Social), e o número de irmãos (com o Apoio Social e as Actividades de Interacção Pais-Filhos). Este estudo levanta ainda algumas considerações no que respeita a importância do apoio prestado às famílias nesta etapa de vida, nomeadamente a criação de redes sociais de ajuda de pessoas mais próximas que permitam aos pais, sentirem-se apoiados no seu papel parental.
The number of drugs with solubility limitations under development has been increasing. Limited aqueous solubility is a major challenge in the development of oral-dosage forms, as it may impact oral ...bioavailability. To circumvent this issue various solubilization strategies have been developed. Two of these strategies are the generation of amorphous solid dispersions and pharmaceutical cocrystals. Amorphous solid dispersions are today one of the most popular solubilization strategies to improve solubility. In contrast, pharmaceutical cocrystals are an emerging technology, but whose acceptance has been increasing in the last years. In this thesis, new computational screening methods to predict drug-polymer kinetic miscibility and in vivo performance were developed to support the early formulation design of amorphous solid dispersions. Regarding the computational tool to predict kinetic miscibility, this consisted on the implementation of a mathematical model that combined thermodynamic, kinetic and process considerations. The novelty of this model is related with its potential to evaluate a ternary system made of drug, polymer and solvent, as well as, the consideration of time dependent phenomena, such as components' diffusion and solvent evaporation. For considering the evaporation of the solvent, the practical utility of this tool was demonstrated for the early development of amorphous dispersions produced by spray drying. The results obtained with the model not only enabled the ranking of the polymers according to their miscibility capacity with the drug, but also the narrowing of an optimal drug load range within which drug-polymer miscibility is guaranteed. In what accounts the computational tool to predict amorphous solid dispersions in vivo performance, this consisted on a statistical model having as input several molecular descriptors of the drug and the polymer, and as output in vivo pharmacokinetic data such as the area under the curve (AUC) and the maximum concentration (Cmax) achieved in the pharmacokinetic profile. The novelty of this model is related to the fact that the experimental in vivo data were obtained from the literature. The results produced generalized performance trends, as well as identified the molecular descriptors with higher influence for the in vivo performance. New and alternative manufacturing methods were also explored in this thesis, for the generation of amorphous solid dispersions and pharmaceutical cocrystals. New technologies that allow the control of the particle size at the nano-scale while maintaining the amorphous state, or technologies with reduced footprint that allow the particle engineering of cocrystals are scarce in the literature. A novel solvent controlled precipitation process based on microfluidization was assessed to produce nano-sized amorphous solid dispersions. Moreover, an experimental design was conducted to study the effect of different formulation variables (viz. polymer type, drug load, and feed solid's concentration) on the particle size and morphology, drug's solid state and drug's molecular distribution within the carrier of the co-precipitated materials produced. Nano-composite aggregated particles were produced after isolation using spray drying. According to the results obtained it was possible to conclude that the particle size of the spray-dried aggregates was dependent on the feed solids' concentration, while the level of aggregation between nanoparticles was dependent on the drug-polymer ratio. Depending on the type of polymeric stabilizer and the drug load in formulation, amorphous nano-solid dispersions or crystalline nano-solid dispersions could be produced. The small particle size at the nano-scale, i.e. the high surface area, was found to be a more important factor than the amorphization of the drug, to enhance the dissolution-rate and in vivo bioavailability of a model drug whose absorption is dissolution-rate limited. Spray congealing was the technology evaluated for the production of cocrystals. The work considered a feasibility study, followed by an experimental design to assess the impact of varying atomization and cooling-related process parameters on cocrystals formation, purity, particle size and shape, and bulk powder flow properties. It was demonstrated that spray congealing could be used to produce cocrystals particles. These were compact and spherical particles consisting of aggregates of individual cocrystals fused or adhered to each other. Varying the process parameters did not influence cocrystals formation, but had an impact on cocrystals purity. Moreover, it was demonstrated that cocrystals particle properties can be adjusted in a single process step, by varying the atomization and cooling efficiency, in order to produce particles more suited for incorporation in the final dosage forms.
Orofacial clefts (OFC) are among the most common birth defects worldwide. The etiology of non-syndromic OFC is still largely unknown. During embryonic development, the cell adhesion molecule ...E-cadherin, encoded by CDH1, is highly expressed in the median edge epithelium of the palate. Furthermore, in multiple families with CDH1 mutations, OFC cases are observed. To determine whether CDH1 is a causative gene for non-syndromic OFC and to assess whether CDH1 mutation screening in non-syndromic OFC patients enables identification of families at risk of cancer, direct sequencing of the full coding sequence of CDH1 was performed in a cohort of 81 children with non-syndromic OFC. Eleven children had heterozygous CDH1 sequence variants, 5 cases with 4 distinct missense mutations and 8 cases with 4 intronic variants. Using a combination of in silico predictions and in vitro functional assays, three missense mutations in four non-syndromic OFC patients were predicted to be damaging to E-cadherin protein function. The intronic variants including one tested in an in vitro assay appeared to be benign, showing no influence on splicing. Functionally relevant heterozygous CDH1 missense mutations were found in 4 out of 81 (5%) patients with non-syndromic OFC. This finding opens a new pathway to reveal the molecular basis of non-syndromic OFC. Cancer risk among carriers of these mutations needs to be defined.
Huntington's disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin's polyglutamine tract. Lowering mutant huntingtin has been proposed ...for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model. Targeted CRISPR-Cas9 editing shows this effect is not due to huntingtin lowering, pointing instead to pseudoexon inclusion in PMS1. Homozygous but not heterozygous inactivation of PMS1 also reduces CAG repeat expansion, supporting PMS1 as a genetic modifier of HD and a potential target for therapeutic intervention. Although splice modulation provides one strategy, genome-wide transcriptomics also emphasize consideration of cell-type specific effects and polymorphic variation at both target and off-target sites.
High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a ...set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Endophytic fungi are a rich source of secondary metabolites. The interactions between endophytes and their hosts lead to the production of several bioactive substances grouped into different classes, ...each having a wide variety of effects against various pathogens. The metabolites obtained from these organisms include steroids, alkaloids, phenols, isocoumarins, xanthones, quinones, and terpenoids, among others. These substances are known to have antibiotic, antiparasitic, antifungal, and antiviral effects. This review summarizes secondary metabolites with antiviral effects produced by endophytic fungi and highlights the importance of research in developing novel antiviral substances. We demonstrate that endophytic fungi are a rich source of secondary metabolites that combat pathologies caused by viruses. Optimizing practical and biotechnological screening tools for the research of these metabolites will provide promising drugs to combat these infections.
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